The compound N,N-dimethyl-9-[3-(4-methyl-1-piperazinyl)-propylidene]thioxanthene-2-sulf onamide (known as "thiothixene"), its non-toxic acid addition salts and hydrates of those salts have considerable utility as psychotherapeutic agents in the chemotherapy of certain mental diseases and disorders, especially the treatment of excited mental states. Of particular interest is "thiothixene hydrochloride", the dihydrate of the dihydrochloride acid addition salt of thiothixene. The cis-stereoisomer of thiothixene (melting point = 145.degree.-147.degree. C.), in which the substituted propylidene group is oriented towards the N,N-dimethylsulfonamide group, is far more active pharmacologically than the trans-isomer (melting point = 123.degree.-125.degree. C.).
N,N-dimethyl-9-[3-(4-methyl-1-piperazinyl)propylidene]-thioxanthene-2-sulfo namide and alternate synthetic methods of preparing it are disclosed in U.S. Pat. Nos. 3,310,553 and 3,354,155. Use of these methods yields a roughly equal mixture of cis- and trans-isomers which, following the teaching of these patents, is converted to isolated cis-isomer by a fractional crystallization method involving repeated partial isomerizations in hydrochloric acid of intermediate crops of trans-isomer. This prior art process for isolating thiothixene in the desired cis-form suffers from several undesirable features: low yield, the need to perform numerous costly and repetitive operations to obtain that yield, the need to precipitate first the undesired steroisomer and then re-dissolve it for conversion to the desired steroisomer, and, finally, the highly unfavorable equilibrium ratio [about 2:1 (trans:cis)] of the aqueous acid steroisomerization of thiothixene. The need for an isomerization/recovery process which would alleviate these undesirable features is manifest.
The conversion of either stereoisomer of a compound of the formula ##STR1## wherein NRR.sup.1 can be a heterocyclic ring and Y is halogen, alkyl, hydroxy, alkoxy, alkylthio, acyl, haloalkyl, or amino, to the other stereoisomer by treatment with strong base in a polar organic solvent is disclosed by British Pat. No. 881,488 and Japanese Pat. No. 12,708 (1965). U.S. Pat. No. 3,115,502 indicates general applicability to all geometrically asymmetric 9-(basically substituted)-thioxanthene compounds. This basic isomerization yields an approximately equimolar mixture of the two stereoisomers at equilibrium. After isolation of a portion of the desired isomer by evaporation and selective crystallization, e.g., from petroleum ether, the remaining material containing an excess of the other isomeric form can be subjected once again to the basic conversion reaction. However, numerous cycles of isomerization, evaporation, dilution, selective crystallization, and evaporation and re-dilution of the mother liquor would be required to obtain a substantial isolated yield of the desired isomer.